Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000541606
Ethics application status
Approved
Date submitted
13/05/2014
Date registered
21/05/2014
Date last updated
22/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Validation of two stable isotopic labels for determination of albumin synthesis rate
Scientific title
Determination of albumin synthesis rate by intravenous infusion of the labeled amino acids d5-phenylalanine versus d8-phenylalanine in healthy volunteers
Secondary ID [1] 284582 0
Nil
Universal Trial Number (UTN)
U1111-1156-7233
Trial acronym
d5d8-albumin
Linked study record

Health condition
Health condition(s) or problem(s) studied:
liver function / liver failure 291873 0
Condition category
Condition code
Metabolic and Endocrine 292223 292223 0 0
Other metabolic disorders
Oral and Gastrointestinal 292275 292275 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Healthy volunteers will repeatedly receive intravenous 10 min infusions of amino acids labeled with stable isotopes to assess albumin and fibrinogen fractional synthesis rates by measuring the increase of labels in the two plasma proteins, respectively. Either d5-phenylalanine (d5-Phe) or d8-phenylalanine (d8-Phe) will be used together with unlabeled phenylalanine (Phe). All infusions will contain a combined amount of labeled and unlabeled phenylalanine of 45 mg/kg body weight dissolved in sterile water to a concentration of 20 mg/ml. Only the proportion between the two labels and Phe will vary between the occasions. No other fluid will be given. All subjects will serve as their own controls.

In protocol 1a, volunteers (n=5) will receive a 10 min infusion of unlabeled Phe with 10 atom percent excess (APE) d5-Phe on day 1. APE is defined as 100*tracer/(tracer+tracee) where unlabled Phe is the tracee. On the second occasion day 3 the 10 min infusion will consist of unlabeled Phe and 10 APE d8-Phe. The combined amount of labeled and unlabeled phenylalanine will be 45 mg/kg body weight on each occasion.

In protocol 1b, volunteers (n=5) will receive a 10 min infusion of unlabeled Phe and 10 APE d8-Phe on day 1. On the second occation day 3 the 10 min infusion will consist of unlabeled Phe and 10 APE d5-Phe. The combined amount of labeled and unlabeled phenylalanine will be 45 mg/kg body weight on each occasion.
In protocol 1, n=10 volunteers will be studied at day 1 and day 3, thus in total receive 2 infusions of mixed labeled and unlabeled phenylalanine.

In protocol 2, volunteers (n=6) will receive a 10 min infusion of unlabeled Phe mixed with 10 APE d5-Phe in the morning of day 1, and, after approximately five hours, on occasion 2 the 10 min infusion will consist of unlabeled Phe with 10 APE d8-Phe. Finally, on the third occasion day 8 the 10 min infusion will consist of unlabeled Phe with 20 APE d5-Phe. The combined amount of labeled and unlabeled phenylalanine will be 45 mg/kg body weight on each occasion. The volunteers in protocol 2 will be studied at day 1 in the morning, day 1 in the afternoon (after approximately 5 hrs), and on day 8, thus in total receive 3 short infusions.

The size of the plasma pool will be determined by anthropometric calculation of plasma volume and plasma-albumin and plasma-fibrinogen, respectively, which makes determination of absolute synthesis rate possible.
Intervention code [1] 289358 0
Diagnosis / Prognosis
Comparator / control treatment
Synthesis rates derived from d5-phenylalanine will be compared to those from d8-phenylalanine. Also repeatability with the same label will be assessed. Volunteers will serve as their own controls.
Control group
Active

Outcomes
Primary outcome [1] 292094 0
albumin synthesis rate

Albumin fractional synthesis rate is assessed by the flooding technique (Ballmer et al Am J Physiol 1990; 259: E797-803). The incorporation of labeled phenylalanine in plasma albumin is assessed by gas chromatography-mass spectrometry after separating albumin from other plasma proteins. The precursor pool is assessed from the ratio of labeled to unlabeled phenylalanine in plasma.
Timepoint [1] 292094 0
In the morning after start of infusion on each study occation. Volunteers will be studied twice (protocol 1) on day 1 and 3, or thrice on day 1, after 5 hrs and after 7 days (protocol 2).
Secondary outcome [1] 308198 0
Fibrinogen synthesis rate

Fibrinogen fractional synthesis rate is assessed by the flooding technique (Ballmer et al Am J Physiol 1990; 259: E797-803). The incorporation of labeled phenylalanine in plasma fibrinogen is assessed by gas chromatography-mass spectrometry after separating fibrinogen from other plasma proteins. The precursor pool is assessed from the ratio of labeled to unlabeled phenylalanine in plasma.
Timepoint [1] 308198 0
In the morning after start of infusion on each study occation. Volunteers will be studied twice (protocol 1) on day 1 and 3, or thrice on day 1, after 5 hrs and after 7 days (protocol 2).

Eligibility
Key inclusion criteria
healthy volunteers
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Age < 18 years
Participation in other trial within 2 months

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Volunteers will be enrolled among previous volunteers or other subjects volunteering to participate in studies at Department of Anesthesiology and Intensive Care at karolinska University Hospital, Huddinge, Sweden
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
With alfa 0.05 and beta 0.80, 8 subjects are necessary to detect a difference corresponding to effect size 1. In a study with repeated meassures of albumin synthesis rate after 6 hrs with the same isotopic label coefficient of variation was 12%. Then a 12% difference is detectable with 80% power by 8 subjects . 10 subjects are planned in protocol 1, and another 6 in protocol 2.
Data will presented as mean +/- sd or median (range) as approprite. When applicable Student´s t-test, ANOVA, Wilcoxon and Friedmman´s ANOVA will be used.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
23/05/2014
Actual
26/05/2014
Date of last participant enrolment
Anticipated
23/12/2014
Actual
6/10/2014
Date of last data collection
Anticipated
Actual
9/10/2014
Sample size
Target
16
Accrual to date
Final
16
Recruitment outside Australia
Country [1] 6047 0
Sweden
State/province [1] 6047 0

Funding & Sponsors
Funding source category [1] 289220 0
Government body
Name [1] 289220 0
Supported by grants provided by the Stockholm County Council (ALF project), grants #531467 and #513126.
Country [1] 289220 0
Sweden
Primary sponsor type
Individual
Name
Jan Wernerman
Address
Karolinska Institutet, Department of Clinical Science, Intervention and Technology (CLINTEC)
and
Dept. Anesthesiology and Intensive Care, B31
Karolinska University Hospital Huddinge
SE-141 86 Stockholm, Sweden
Country
Sweden
Secondary sponsor category [1] 287901 0
None
Name [1] 287901 0
Address [1] 287901 0
Country [1] 287901 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290988 0
Regional Ethical Board in Stockholm
Ethics committee address [1] 290988 0
Ethics committee country [1] 290988 0
Sweden
Date submitted for ethics approval [1] 290988 0
Approval date [1] 290988 0
30/10/2013
Ethics approval number [1] 290988 0
2013/1742-31/4

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 48298 0
Prof Jan Wernerman
Address 48298 0
Karolinska Institutet, Department of Clinical Science, Intervention and Technology (CLINTEC)
and
Dept. Anesthesiology and Intensive Care, B31
Karolinska University Hospital Huddinge
SE-141 86 Stockholm, Sweden
Country 48298 0
Sweden
Phone 48298 0
+46 8 58 58 00 00
Fax 48298 0
Email 48298 0
[email protected]
Contact person for public queries
Name 48299 0
Ake Norberg
Address 48299 0
Karolinska Institutet, Department of Clinical Science, Intervention and Technology (CLINTEC)
and
Dept. Anesthesiology and Intensive Care, B31
Karolinska University Hospital Huddinge
SE-141 86 Stockholm, Sweden
Country 48299 0
Sweden
Phone 48299 0
+46 8 58 58 00 00
Fax 48299 0
+ 46 8 779 54 24
Email 48299 0
[email protected]
Contact person for scientific queries
Name 48300 0
Ake Norberg
Address 48300 0
Karolinska Institutet, Department of Clinical Science, Intervention and Technology (CLINTEC)
and
Dept. Anesthesiology and Intensive Care, B31
Karolinska University Hospital Huddinge
SE-141 86 Stockholm, Sweden
Country 48300 0
Sweden
Phone 48300 0
+46 8 58 58 00 00
Fax 48300 0
Email 48300 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseRepeated quantitative measurements of de Novo synthesis of albumin and fibrinogen.2017https://dx.doi.org/10.1371/journal.pone.0174611
N.B. These documents automatically identified may not have been verified by the study sponsor.